rs761232237

Variant names:

• chr3-13504513-C-G
• rs761232237
• NM_024827.4:c.874C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-13504513-C-G
• chr3-13504513-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024827.4(HDAC11):​c.874C>G​(p.Arg292Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R292C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HDAC11 NM_024827.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

Genes affected

HDAC11 (HGNC:19086): (histone deacetylase 11) This gene encodes a class IV histone deacetylase. The encoded protein is localized to the nucleus and may be involved in regulating the expression of interleukin 10. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34093463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC11	NM_024827.4	c.874C>G	p.Arg292Gly	missense_variant	Exon 10 of 10	ENST00000295757.8	NP_079103.2
HDAC11	NM_001136041.3	c.721C>G	p.Arg241Gly	missense_variant	Exon 10 of 10		NP_001129513.1
HDAC11	NM_001330636.2	c.637C>G	p.Arg213Gly	missense_variant	Exon 7 of 7		NP_001317565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC11	ENST00000295757.8	c.874C>G	p.Arg292Gly	missense_variant	Exon 10 of 10	1	NM_024827.4	ENSP00000295757.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.30	T;T;T;T;.;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.80	T;T;T;T;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.34	T;T;T;T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Pathogenic	3.4	M;.;.;.;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Pathogenic	-4.6	D;D;D;D;D;D
REVEL	Benign	0.20
Sift4G	Benign	0.25	.;.;.;.;T;T
Polyphen		0.46	P;.;.;.;.;.
Vest4		0.28
MutPred		0.52		Loss of methylation at R292 (P = 0.0291);.;.;.;.;.;
MVP		0.78
MPC		0.89
ClinPred		0.75	D
GERP RS		2.5
Varity_R		0.60
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs761232237; hg19: chr3-13546013;